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Who's on First? CML Drug May Take Starting Position

That’s what M. D. Anderson investigators reported at the American Society of Clinical Oncology’s annual meeting in June.

Jorge Cortes, M.D., and Fe Calda, R.N., hope that a second-line drug for chronic myelogenous leukemia will become the next frontline therapy for the disease.

Researchers are encouraged by early results from an investigational drug study showing that dasatinib – an established second-line drug for chronic myelogenous leukemia – has high response rates when given to newly diagnosed patients as their first therapy for the disease.

Led by Jorge Cortes, M.D., professor in M. D. Anderson’s Department of Leukemia, investigators found that patients taking dasatinib achieved complete cytogenetic response – absence of the abnormal chromosome that drives this disease – more rapidly than what has been observed historically using the current frontline therapy. Dasatinib in these patients, they observed, also appeared to be well tolerated.

Produced by Bristol-Myers Squibb, dasatinib (Sprycel™) was approved by the U.S. Food and Drug Administration in 2006 for use in patients whose disease is unresponsive to or becomes resistant to the frontline therapy imatinib. Both drugs bind to and block a genetically flawed protein known as BCR-ABL, which causes the disease. A key benefit of dasatinib, investigators note, is that it’s active against many imatinib-resistant BCR-ABL mutations.

Investigators hypothesize that using dasatinib first will produce an earlier response, which may translate to a better overall survival. While this hasn’t been proven yet, they say these early results are encouraging.

Thirty-five patients who enrolled in the Phase II clinical trial between November 2005 and December 2006 were evaluated. These patients received either 100 mg of dasatinib once daily or 50 mg twice daily.

Thirty-four patients had been on the clinical trial for at least three months when Cortes and his team evaluated their data. They found that 77% of patients at three months, 92% at six months and 95% at one year had a complete cytogenetic response.

This rapid response compares favorably to historical data on patients at M. D. Anderson who took imatinib (Gleevec®) as a first therapy. Produced by Novartis, imatinib’s complete response rates at six months are 54% at 400 mg daily and 85% for 800 mg daily. However, at 12 months 72% of patients receiving 400 mg of imatinib and 92% of those receiving 800 mg had a complete cytogenetic response.

The dasatinib clinical trial, which is set to enroll 100 patients, remains in progress with more than 30 patients currently participating.

The comparison to historical data provides insight into dasatinib’s effect, Cortes notes, but a randomized clinical trial comparing medications directly would present a more detailed picture.